Medical devices manufactured from latex: European regulatory initiatives.

In Europe the marketing of medical devices manufactured from latex is regulated by directives describing the essential (safety) requirements that products have to fulfill to obtain marketing approval. This paper describes the general requirements for marketing medical devices in Europe and, more specifically, the requirements for products manufactured from natural rubber latex. The requirements for marketing medical devices can be fulfilled by using the relevant harmonized European standards. These standards are regularly under revision to incorporate the latest scientific developments. For certain devices, for example, latex medical (examination and surgical) gloves, specific standards have been published. Medical devices manufactured from latex pose a serious problem because of the risk of induction of allergy both against the latex proteins inherently present (type I or immediate type allergy) and against chemicals added during processing (type IV or delayed type hypersensitivity) present as residues in the latex products. So, besides requirements for product quality in terms of barrier properties, strength, and sterility, the main focus consists of the allergy-inducing properties of the latex products. Recent developments have reopened the discussion on the value of total protein versus allergen determination in latex medical gloves. However, as long as minimal levels needed for both sensitization and elicitation have not been established, a safe maximum level for leachable proteins/allergens in latex products cannot be determined. A European Commission guidance document on the latex allergy problem is currently being drafted by experts from Competent Authorities.

Risk assessment of dithiocarbamate accelerator residues in latex-based medical devices: genotoxicity considerations.

The Medical Devices Agency (MDA) has investigated potential human health hazards arising from the presence of dithiocarbamate vulcanization accelerators in latex products (mainly gloves). After collection of manufacturer's data on usage and residues of these accelerators, an independent investigation of solvent extractable residues and dithiocarbamate migration into aqueous simulants was commissioned, to complement equivalent "in-house" test data from two major manufacturers. The presence of extractable accelerator residues in commercial products was confirmed. Potential human health hazards associated with dithiocarbamates include genotoxicity and possible carcinogenicity: a review of published data was conducted to evaluate the evidence for this, with particular reference to three zinc dithiocarbamates with significant commercial usage (ZDMC, ZDEC and ZDBC: see Fig. 1). Data gaps were identified, and mutagenicity studies commissioned to fill these. These studies comprised tests both in vitro (bacterial and L5178Y cell gene mutation, cultured lymphocyte chromosome aberration) and in vivo (mouse bone marrow micronucleus, rat liver UDS). It is concluded that ZDMC must be considered a genotoxin (and thus a probable carcinogen): residues of this substance in latex medical devices should be minimized. ZDEC proved genotoxic in vitro but was not clearly genotoxic in vivo, and may have activity intermediate between that of ZDMC and that of ZDBC, which showed at most weak activity in a single in vitro (chromosome aberration) test. It is proposed that the use of ZDBC as a vulcanization accelerator in the manufacture of latex gloves, rather than ZDEC, ZDMC or their precursors, would reduce or remove the health concerns arising from accelerator residues.

Dietary carotenoids protect human cells from damage.

A physical chemistry technique based on singlet oxygen luminescence at about 1270 nm and a biological cell membrane technique were used to study the quenching of singlet oxygen by four carotenoids bound to the surface of lymphoid cells. All the carotenoids studied showed a beneficial effect in cell protection, but there were subtle differences between them.

Breast implants: is there an association with connective tissue disease?

Following concern over a suggested link between the implantation of silicone gel and connective tissue disease, the Medical Devices Directorate (MDD) of the Department of Health reviewed all available data for submission to a specially convened Expert Advisory Group. Animal studies indicated that silicones are unlikely to stimulate a specific antibody response or cell-mediated immunity, that they have no adverse effect on resistance to infection, and produce minimal effects in the presence of potent adjuvants but can act as adjuvants themselves. The connective tissue disease most commonly claimed to be associated with breast implants is scleroderma. Although one series of patients showed a significantly higher prevalence of this disease than expected, there is no clear indication that the incidence of scleroderma in women with breast implants is any higher than in the general population.